The importance of various putative Bordetella pertussis cell adhesins which mediate the adherence of the bacteria to mammalian cells is being investigated. We have demonstrated that pertactin, a 69 kDa surface protein, can promote the adherence of Chinese hamster ovary (CHO) cells. We have also shown that another surface protein, filamentous hemagglutinin (FHA) can also independently promote the adherence of mammalian cells. To investigate the mechanism of attachment of these protein to their cell receptor, we have studied the role of the sequence Arginine-Glycine-Aspartic Acid (RGD), which is a sequence found in pertactin and FHA, in mediating cell adherence. The adherence of CHO cells to pertactin occurs via an RGD binging site on the protein. The RGD sequence does not seem to be involved in the interaction of CHO cells to FHA, a lectin-like interaction seems more probable to be to mechanism of cell interaction used by this protein. It has recently been shown that B. pertussis can invade and survive within mammalian cells. Peptides homologous to the RGD sequence from pertactin can inhibit invasion of the bacteria. The peptides derived from the sequence of FHA with RGD had no effect on invasion. We have further demonstrated the role of FHA and pertactin in attachment and invasion by coating the noninvasive Staphilococus aureus bacteria with purified pertactin or FHA and quantitating the amount of colony forming units found internalized in HeLa cells. Specific RGD-containing peptide inhibhtion of invasion was achieved with pertactin-coated S. Aureus.